Insights into innate immune and inflammatory response resulting from neurotropic virus infections in a neural spheroid organotypic model elucidated through transcriptome and cytokine profiling 2292

Description Neurotropic virus infections are a continuous threat to public health as severe neuroinflammation leads to acute and chronic illnesses with potential lifelong neurological sequelae or even death. Varying degrees of neuropathologies have been associated with viral infection by many arboviruses, including members of the Peribunyaviridae and Togaviridae families. The lack of approved antiviral therapeutics against these viruses has underscored the need for understanding the molecular mechanisms and cellular responses underlaying severe disease caused by infection in the brain. Microglia and astrocyte cell populations play a key role in immune and inflammatory cell responses, synaptogenesis and support of neuronal function, making these cells crucial to integrate into in vitro models to address key questions regarding complex cell defense processes against viruses. We utilized our induced pluripotent stem cell (iPSC-) derived brain-region specific human neural spheroid platform to investigate neurotropic viral infection and disease in a human-relevant tissue-based platform, allowing us to explore both cell-virus interactions and response to infection. We evaluated La Crosse virus (LACV) and Chikungunya virus (CHIKV) and describe the virus mediated disruption of the spheroid’s neural activity profiles then, using transcriptome and secreted cytokine profiling we investigated the changes induced by infection in these neural spheroids to evaluate innate immune mechanisms of defense. Funding Sources NIH Intramural Research Program, TR000437. Topic Categories Viral Immunology (VIR)